In Vivo Modulation of Nogo-B Attenuates Neointima Formation

Kritz Wilson, A.B., Yu, J., Wright, P.L., Wan, S., George, S.J., Halliday, C., Kang, N., Sessa, W.C. and Baker, A.H. (2008) In Vivo Modulation of Nogo-B Attenuates Neointima Formation. Molecular Therapy, 16(11), pp. 1798-1804. (doi: 10.1038/mt.2008.188)

Abstract

Nogo-B was recently identified as a novel vascular marker; the normally high vascular expression of Nogo-B is rapidly lost following vascular injury. Here we assess the potential therapeutic effects of Ad-Nogo-B delivery to injured vessels in vivo. Nogo-B overexpression following Ad-Ng-B infection of vascular smooth muscle cells (VSMCs) was shown to block proliferation and migration in a dose-dependent manner in vitro. We next assessed the effects of Ad-Ng-B treatment on neointima formation in two in vivo models of acute vascular injury. Adventitial delivery of Ad-Ng-B to wire-injured murine femoral arteries led to a significant decrease in the intimal area [0.014 mm(2) versus 0.030 mm(2) (P = 0.049)] and the intima: media ratio [0.78 versus 1.67 (P = 0.038)] as compared to the effects of Ad-beta-Gal control virus at 21 days after injury. Similarly, lumenal delivery of Ad-Ng-B to porcine saphenous veins prior to carotid artery grafting significantly reduced the intimal area [2.87 mm(2) versus 7.44 mm(2) (P = 0.0007)] and the intima: media ratio [0.32 versus 0.55 (P = 0.0044)] as compared to the effects following the delivery of Ad-beta-Gal, at 28 days after grafting. Intimal VSMC proliferation was significantly reduced in both the murine and porcine disease models. Gene delivery of Nogo-B exerts a positive effect on vascular injury-induced remodeling and reduces neointimal development in two arterial and venous models of vascular injury

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kritz Wilson, Dr Angelika and Baker, Professor Andrew
• Authors: Kritz Wilson, A.B., Yu, J., Wright, P.L., Wan, S., George, S.J., Halliday, C., Kang, N., Sessa, W.C., and Baker, A.H.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Molecular Therapy
• ISSN: 1525-0016